Abstract
Pristimerin is a quinonemethide triterpenoid that has shown anticancer activity against some cancer types. However, the antitumor effects of pristimerin (PM) in ovarian cancer cells have not been adequately studied. The objective of the present study was to determine the anticancer activity and its mechanism of action in human ovarian carcinoma cell lines. PM strongly inhibited the proliferation of ovarian cancer cells by inducing apoptosis characterized by increased annexin V-binding, cleavage of poly (ADPribose) polymerase (PARP-1) and procaspases-3, -8 and -9. Furthermore, PM caused mitochondrial depolarization. Western blot analysis showed inhibition of prosurvival phospho-AKT (p-AKT), nuclear factor kappa B (NF-κB) (p65) and phospho- mammalian target of rapamycin (p-mTOR) signaling proteins in cells treated with PM. Treatment with PM also inhibited the expression of NF-κB-regulated antiapoptotic Bcl-2, Bcl-xL, c-IAP1 and survivin. Thus, our data showing potent antiproliferative and apoptosis-inducing activity of PM in ovarian carcinoma cells through the inhibition of AKT/NF-κB/mTOR signaling pathway warrant further investigation of PM for the management of ovarian cancer.
Original language | English (US) |
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Pages (from-to) | 275-283 |
Number of pages | 9 |
Journal | Journal of Experimental Therapeutics and Oncology |
Volume | 10 |
Issue number | 4 |
State | Published - 2014 |
Externally published | Yes |
Keywords
- Akt
- Apoptosis
- Nf-κb
- Ovarian cancer
- Pristimerin
- mTOR
ASJC Scopus subject areas
- Pharmacology
- Drug Discovery
- Cancer Research